IFNγ at the early stage induced after cryo-thermal therapy maintains CD4 Th1-prone differentiation, leading to long-term antitumor immunity.

Introduction: Recently, more and more research illustrated the importance of inducing CD4 T helper type (Th)-1 dominant immunity for the success of tumor immunotherapy. Our prior studies revealed the crucial role of CD4 Th1 cells in orchestrating systemic and durable antitumor immunity, which contributes to the satisfactory outcomes of the novel cryo-thermal therapy in the B16F10 tumor model. However, the mechanism for maintaining the cryo-thermal therapy-mediated durable CD4 Th1-dominant response remains uncovered.

Relevance of Protein Intake for Weaning in the Mechanically Ventilated Critically Ill: Analysis of a Large International Database.

Objectives: The association between protein intake and the need for mechanical ventilation (MV) is controversial. We aimed to investigate the associations between protein intake and outcomes in ventilated critically ill patients.

Design: Analysis of a subset of a large international point prevalence survey of nutritional practice in ICUs.

Sensory Stimulation as a Means of Sustained Enhancement of Well-Being in Leopard Geckos, (Eublepharidae, Squamata).

Although the private keeping of reptiles has boomed in most western countries since the millennium, studies dealing with the recognition and promotion of welfare in these reptiles seem to represent a blind spot of scientific attention. The vast majority of studies from the field of animal welfare science still concern mammals and birds. The leopard gecko is probably the most common lizard that is kept in domestic terrariums worldwide.

The Prospective COVID-19 Post-Immunization Serological Cohort in Munich (KoCo-Impf): Risk Factors and Determinants of Immune Response in Healthcare Workers.

Antibody studies analyze immune responses to SARS-CoV-2 vaccination and infection, which is crucial for selecting vaccination strategies. In the KoCo-Impf study, conducted between 16 June and 16 December 2021, 6088 participants aged 18 and above from Munich were recruited to monitor antibodies, particularly in healthcare workers (HCWs) at higher risk of infection. Roche Elecsys Anti-SARS-CoV-2 assays on dried blood spots were used to detect prior infections (anti-Nucleocapsid antibodies) and to indicate combinations of vaccinations/infections (anti-Spike antibodies).

Two-stage generative adversarial networks for metal artifact reduction and visualization in ablation therapy of liver tumors.

Purpose: The strong metal artifacts produced by the electrode needle cause poor image quality, thus preventing physicians from observing the surgical situation during the puncture process. To address this issue, we propose a metal artifact reduction and visualization framework for CT-guided ablation therapy of liver tumors.

Methods: Our framework contains a metal artifact reduction model and an ablation therapy visualization model.

Exploration of the impact of multimode thermal therapy versus radiofrequency ablation on CD8 T effector cells of liver malignancies based on single cell transcriptomics.

Introduction: Multimode thermal therapy (MTT) is an innovative interventional therapy developed for the treatment of liver malignancies. When compared to the conventional radiofrequency ablation (RFA), MTT typically offers improved prognosis for patients. However, the effect of MTT on the peripheral immune environment and the mechanisms underlying the enhanced prognosis have yet to be explored.

Survival Analysis for Multimode Ablation Using Self-Adapted Deep Learning Network Based on Multisource Features.

Novel multimode thermal therapy by freezing before radio-frequency heating has achieved a desirable therapeutic effect in liver cancer. Compared with surgical resection, ablation treatment has a relatively high risk of tumor recurrence. To monitor tumor progression after ablation, we developed a novel survival analysis framework for survival prediction and efficacy assessment.

Activated NK cells reprogram MDSCs via NKG2D-NKG2DL and IFN-γ to modulate antitumor T-cell response after cryo-thermal therapy.

Background: Myeloid-derived suppressor cells (MDSCs) can potently inhibit T-cell activity, promote growth and metastasis of tumor and contribute to resistance to immunotherapy. Targeting MDSCs to alleviate their protumor functions and immunosuppressive activities is intimately associated with cancer immunotherapy. Natural killer (NK) cells can engage in crosstalk with multiple myeloid cells to alter adaptive immune responses, triggering T-cell immunity.

Combining all-trans retinoid acid treatment targeting myeloid-derived suppressive cells with cryo-thermal therapy enhances antitumor immunity in breast cancer.

Targeting myeloid-derived suppressive cells (MDSCs) has been considered a potential strategy in tumor therapy. However, a single drug targeting MDSCs remains a challenge in the clinic. An increasing number of studies have shown that combination agents targeting MDSCs and immunotherapy may provide exciting new insights and avenues to explore in tumor therapy.

Combination of polythyleneimine regulating autophagy prodrug and Mdr1 siRNA for tumor multidrug resistance.

Multidrug resistance (MDR) has been restricting the efficacy of chemotherapy, which mainly include pump resistance and non-pump resistance. In order to fight overall MDR, a novel targeted gene/drug co-deliver nano system is developed, which can suppress the drug efflux pumps and modulate autophagy to overcoming both pump and non-pump resistance. Here, small interfere RNA (siRNA) is incorporated into polymer-drug conjugates (PEI-PTX, PP) which are composed of polyethyleneimine (PEI) and paclitaxel (PTX) via covalent bonds, and hyaluronic acid (HA) is coated on the surface of PP/siRNA to achieve long blood cycle and CD44-targeted delivery.

Th1-Dominant CD4 T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal Therapy.

Recent studies suggest that highly activated, polyfunctional CD4 T cells are incredibly effective in strengthening and sustaining overall host antitumor immunity, promoting tumor-specific CD4 T-cell responses and effectively enhancing antitumor immunity by immunotherapy. Previously, we developed a novel cryo-thermal therapy for local tumor ablation and achieved long-term survival rates in several tumor models. It was discovered that cryo-thermal therapy remodeled the tumor microenvironment and induced an antigen-specific CD4 T-cell response, which mediated stronger antitumor immunity .

CCL5 Deficiency Enhanced Cryo-Thermal-Triggered Long-Term Anti-Tumor Immunity in 4T1 Murine Breast Cancer.

Breast cancer remains one of the most common solid tumors. Tumor immunosuppressive factors mainly hinder the control of tumors. We previously developed an innovative cryo-thermal therapy that was shown to significantly suppress distal metastasis and improve long-term survival in murine B16F10 melanoma and 4T1 mammary carcinoma models.

A Novel Multi-Mode Thermal Therapy for Colorectal Cancer Liver Metastasis: A Pilot Study.

A novel multi-mode thermal therapy was developed for local tumor ablation and the systemic stimulation of anti-tumor immunity, consisting of a rapid liquid nitrogen freezing, and followed by the radiofrequency heating of target tumor tissue. This pilot study aimed to compare the therapeutic effects of the new therapy with conventional radiofrequency ablation (RFA) on patients with colorectal cancer liver metastasis (CRCLM). From August 2016 to September 2019, thirty-one patients with CRCLM received either multi-mode thermal therapy ( = 17) or RFA ( = 14).

Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors.

In recent years, the incidence of various types of tumors has gradually increased, and it has also been found that there is a certain correlation between abnormal glucose and lipid metabolism and tumors. Glycolipid metabolism can promote tumor progression through multiple pathways, and the expression of related genes also directly or indirectly affects tumor metabolism, metastasis, invasion, and apoptosis. There has been much research on targeted drug delivery systems designed for abnormal glucose and lipid metabolism due to their accuracy and efficiency when used for tumor therapy.

A Novel Tumor Progression Prediction Method for Multimode Ablation Treatment.

Objective: The multimode ablation of liver cancer, which uses radio-frequency heating after a pre-freezing process to treat the tumor, has shown significantly improved therapeutic effects and enhanced anti-tumor immune response. Unlike open surgery, the ablated lesions remain in the body after treatment, so it is critical to assess the immediate outcome and to monitor disease status over time. Here we propose a novel tumor progression prediction method for simultaneous postoperative evaluation and prognosis analysis.

Downregulated TNF-α Levels after Cryo-Thermal Therapy Drive Tregs Fragility to Promote Long-Term Antitumor Immunity.

Immunotherapy has emerged as a therapeutic pillar in tumor treatment, but only a minority of patients get benefit. Overcoming the limitations of immunosuppressive environment is effective for immunotherapy. Moreover, host T cell activation and longevity within tumor are required for the long-term efficacy.

Numerical Study of Bubble Cloud and Thermal Lesion Evolution During Acoustic Droplet Vaporization Enhanced HIFU Treatment.

Acoustic droplet vaporization (ADV) has been proven to enhance high intensity focused ultrasound (HIFU) thermal ablation of tumor. It has also been demonstrated that triggering droplets before HIFU exposure could be a potential way to control both the size and the shape of the thermal lesion. In this paper, a numerical model is proposed to predict the thermal lesion created in ADV enhanced HIFU treatment.

Chemosensitivity enhanced by autophagy inhibition based on a polycationic nano-drug carrier.

In recent years, with the increasing understanding of the role of autophagy in tumorigenesis and development, a steady stream of studies have demonstrated that both excessive induction and inhibition of autophagy could effectively improve the therapeutic efficacy against tumors during cytotoxic or molecularly targeted drug therapy. Among them, autophagy inhibition mediated by nanomaterials has become an appealing notion in nanomedicine therapeutics, since it can be exploited as an effective adjuvant in chemotherapy or as a potential anti-tumor agent. Herein, we constructed a pH-sensitive nanoplatform loaded with epirubicin (EPI) (mPEG--P(DPA--DMAEMA)/EPI), enabling effective autophagy inhibition in the process of tumor-targeting therapy and further sensitized the tumors to EPI.

Cell-mediated targeting drugs delivery systems.

Drug delivery systems have shown tremendous promise to improve the diagnostic and therapeutic effects of drugs due to their special property. Targeting tissue damage, tumors, or drugs with limited toxicity at the site of infection is the goal of successful pharmaceuticals. Targeted drug delivery has become significantly important in enhancing the pharmaceutical effects of drugs and reducing their side effects of therapeutics in the treatment of various disease conditions.

A New Model for Estimation of Individual Blood Flow Effect during Multimode Thermal Therapy of Tumor.

An accurate temperate control is the key during multimode thermal therapy of tumor. However, the tumor tissue temperature is greatly influenced by local blood flow changes of individuals. A simple but effective method is proposed for estimation of the local blood flow and its impact on the ablation boundary temperature.

Neoantigen-specific CD4 T-cell response is critical for the therapeutic efficacy of cryo-thermal therapy.

Background: Traditional tumor thermal ablations, such as radiofrequency ablation (RFA) and cryoablation, can result in good local control of tumor, but traditional tumor thermal ablations are limited by poor long-term survival due to the failure of control of distal metastasis. Our previous studies developed a novel cryo-thermal therapy to treat the B16F10 melanoma mouse model. Long-term survival and T-cell-mediated durable antitumor immunity were achieved after cryo-thermal therapy, but whether tumor antigen-specific T-cells were augmented by cryo-thermal therapy was not determined.

Mechanism Investigation of Hyaluronidase-Combined Multistage Nanoparticles for Solid Tumor Penetration and Antitumor Effect.

Background: Hyaluronic acid (HA) is a major component of extracellular matrix (ECM) and its over expression in tumor tissues contributes to the increase of interstitial fluid pressure (IFP) and hinders the penetration of nanoparticles into solid tumors.

Materials And Methods: We here reported a tumoral microenvironment responsive multistage drug delivery system (NPs-EPI/HAase) which was formed layer by layer via electrostatic interaction with epirubicin (EPI)-loaded PEG-b-poly(2-(diisopropylamino)ethyl methacrylate)-b-poly(2-guanidinoethylmethacrylate) (mPEG-PDPA-PG, PEDG) micelles (NPs-EPI) and hyaluronidase (HAase). In this paper, we focused on the hyaluronidase-combined nanoparticles (NPs-EPI/HAase) for tumor penetration in tumor spheroid and solid tumor models in vitro and in vivo.

Overcoming Multiple Absorption Barrier for Insulin Oral Delivery Using Multifunctional Nanoparticles Based on Chitosan Derivatives and Hyaluronic Acid.

Background: Although dynamics and uses of modified nanoparticles (NPs) as orally administered macromolecular drugs have been researched for many years, measures of molecule stability and aspects related to important transport-related mechanisms which have been assessed in vivo remain as relatively under characterized. Thus, our aim was to develop a novel type of oral-based delivery system for insulin and to overcome barriers to studying the stability, transport mechanisms, and efficacy in vivo of the delivery system.

Methods: NPs we developed and tested were composed of insulin (INS), dicyandiamide-modified chitosan (DCDA-CS), cell-penetrating octaarginine (r8), and hydrophilic hyaluronic acid (HA) and were physically constructed by electrostatic self-assembly techniques.